IRE1: a ser/thr protein kinase that possess endonuclease activity. Important in altering gene expression as a response to endoplasmic reticulum based stress signals. Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain, which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis. The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain. Ubiquitously expressed. High levels observed in pancreatic tissue. Functionally connected with insulin biosynthesis in pancreatic beta cells. Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of IRE1.
Protein type: Endoplasmic reticulum; Apoptosis; Chaperone; Kinase, protein; EC 2.7.11.1; Ribonuclease; Protein kinase, Ser/Thr (non-receptor); Membrane protein, integral; Protein kinase, Other; Other group; IRE family
Chromosomal Location of Human Ortholog: 17q24.2
Cellular Component: endoplasmic reticulum membrane; mitochondrion; endoplasmic reticulum; cytoplasm; nuclear inner membrane; integral to endoplasmic reticulum membrane
Molecular Function: endoribonuclease activity; identical protein binding; protein serine/threonine kinase activity; protein binding; protein homodimerization activity; enzyme binding; magnesium ion binding; ADP binding; ATP binding
Biological Process: transcription, DNA-dependent; unfolded protein response; RNA splicing; protein amino acid autophosphorylation; positive regulation of RNA splicing; protein amino acid phosphorylation; unfolded protein response, activation of signaling protein activity; cellular protein metabolic process; regulation of transcription, DNA-dependent; endothelial cell proliferation; UFP-specific transcription factor mRNA processing during unfolded protein response; mRNA catabolic process; cell cycle arrest; regulation of macroautophagy; mRNA cleavage
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